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Publication
Lung Microbiota Contribute to Pulmonary Inflammation and Disease Progression in
Pulmonary Fibrosis.
Authors O'Dwyer DN, Ashley SL, Gurczynski SJ, Xia M, Wilke C, Falkowski NR, Norman KC,
Arnold KB, Huffnagle GB, Salisbury ML, Han MK, Flaherty KR, White ES, Martinez
FJ, Erb-Downward JR, Murray S, Moore BB, Dickson RP
Submitted By Submitted Externally on 4/30/2020
Status Published
Journal American journal of respiratory and critical care medicine
Year 2019
Date Published 5/1/2019
Volume : Pages 199 : 1127 - 1138
PubMed Reference 30789747
Abstract Rationale: Idiopathic pulmonary fibrosis (IPF) causes considerable global
morbidity and mortality, and its mechanisms of disease progression are poorly
understood. Recent observational studies have reported associations between lung
dysbiosis, mortality, and altered host defense gene expression, supporting a
role for lung microbiota in IPF. However, the causal significance of altered
lung microbiota in disease progression is undetermined. Objectives: To examine
the effect of microbiota on local alveolar inflammation and disease progression
using both animal models and human subjects with IPF. Methods: For human
studies, we characterized lung microbiota in BAL fluid from 68 patients with
IPF. For animal modeling, we used a murine model of pulmonary fibrosis in
conventional and germ-free mice. Lung bacteria were characterized using 16S rRNA
gene sequencing with novel techniques optimized for low-biomass sample load.
Microbiota were correlated with alveolar inflammation, measures of pulmonary
fibrosis, and disease progression. Measurements and Main Results: Disruption of
the lung microbiome predicts disease progression, correlates with local host
inflammation, and participates in disease progression. In patients with IPF,
lung bacterial burden predicts fibrosis progression, and microbiota diversity
and composition correlate with increased alveolar profibrotic cytokines. In
murine models of fibrosis, lung dysbiosis precedes peak lung injury and is
persistent. In germ-free animals, the absence of a microbiome protects against
mortality. Conclusions: Our results demonstrate that lung microbiota contribute
to the progression of IPF. We provide biological plausibility for the hypothesis
that lung dysbiosis promotes alveolar inflammation and aberrant repair.
Manipulation of lung microbiota may represent a novel target for the treatment
of IPF.




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